Back to Search Start Over

Promoter methylation of the MGAT3 and BACH2 genes correlates with the composition of the immunoglobulin G glycome in inflammatory bowel disease

Authors :
Marija Klasić
Dora Markulin
Aleksandar Vojta
Ivana Samaržija
Ivan Biruš
Paula Dobrinić
Nicholas T. Ventham
Irena Trbojević-Akmačić
Mirna Šimurina
Jerko Štambuk
Genadij Razdorov
Nicholas A. Kennedy
Jack Satsangi
Ana M. Dias
Salome Pinho
Vito Annese
Anna Latiano
Renata D’Inca
IBD consortium
Gordan Lauc
Vlatka Zoldoš
Source :
Clinical Epigenetics, Vol 10, Iss 1, Pp 1-14 (2018)
Publication Year :
2018
Publisher :
BMC, 2018.

Abstract

Abstract Background Many genome- and epigenome-wide association studies (GWAS and EWAS) and studies of promoter methylation of candidate genes for inflammatory bowel disease (IBD) have demonstrated significant associations between genetic and epigenetic changes and IBD. Independent GWA studies have identified genetic variants in the BACH2, IL6ST, LAMB1, IKZF1, and MGAT3 loci to be associated with both IBD and immunoglobulin G (IgG) glycosylation. Methods Using bisulfite pyrosequencing, we analyzed CpG methylation in promoter regions of these five genes from peripheral blood of several hundred IBD patients and healthy controls (HCs) from two independent cohorts, respectively. Results We found significant differences in the methylation levels in the MGAT3 and BACH2 genes between both Crohn’s disease and ulcerative colitis when compared to HC. The same pattern of methylation changes was identified for both genes in CD19+ B cells isolated from the whole blood of a subset of the IBD patients. A correlation analysis was performed between the MGAT3 and BACH2 promoter methylation and individual IgG glycans, measured in the same individuals of the two large cohorts. MGAT3 promoter methylation correlated significantly with galactosylation, sialylation, and bisecting GlcNAc on IgG of the same patients, suggesting that activity of the GnT-III enzyme, encoded by this gene, might be altered in IBD. The correlations between the BACH2 promoter methylation and IgG glycans were less obvious, since BACH2 is not a glycosyltransferase and therefore may affect IgG glycosylation only indirectly. Conclusions Our results suggest that epigenetic deregulation of key glycosylation genes might lead to an increase in pro-inflammatory properties of IgG in IBD through a decrease in galactosylation and sialylation and an increase of bisecting GlcNAc on digalactosylated glycan structures. Finally, we showed that CpG methylation in the promoter of the MGAT3 gene is altered in CD3+ T cells isolated from inflamed mucosa of patients with ulcerative colitis from a third smaller cohort, for which biopsies were available, suggesting a functional role of this glyco-gene in IBD pathogenesis.

Subjects

Subjects :
Medicine
Genetics
QH426-470

Details

Language :
English
ISSN :
18687075 and 18687083
Volume :
10
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Clinical Epigenetics
Publication Type :
Academic Journal
Accession number :
edsdoj.02961e66a74e88a9665fdbec09eb1d
Document Type :
article
Full Text :
https://doi.org/10.1186/s13148-018-0507-y